Autor: |
Zhou Y; Department of Ultrasonography, Nanjing First Hospital, Nanjing Medical University, Nanjing, China., Tang W; Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences; Nhc Key Laboratory of Living Donor Liver Transplantation, Hepatobiliary Center, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China., Zhuo H; Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences; Nhc Key Laboratory of Living Donor Liver Transplantation, Hepatobiliary Center, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China., Zhu D; Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences; Nhc Key Laboratory of Living Donor Liver Transplantation, Hepatobiliary Center, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China., Rong D; Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences; Nhc Key Laboratory of Living Donor Liver Transplantation, Hepatobiliary Center, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China., Sun J; Department of Nuclear Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China., Song J; Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences; Nhc Key Laboratory of Living Donor Liver Transplantation, Hepatobiliary Center, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China. |
Abstrakt: |
Chemoresistance in hepatocellular carcinoma (HCC) has been found to be influenced by exosomal transport of circRNAs. However, the role of circZFR in HCC chemoresistance still remains unclear. In the present study, circZFR was highly expressed in cisplatin (DDP)-resistant HCC cell lines and could regulate DDP resistance of the HCC cells. Also, circZFR was highly expressed in cancer-associated fibroblast (CAFs) and the exosome of CAFs. In addition, supplementation of CAFs in culture medium could promote DDP resistance of HCC cells. In vivo tumor xenograft experiments showed that knockdown of circZFR inhibited tumor growth and weakened DDP resistance, while CAFs-derived exosomes incubation increased the expression of circZFR, inhibited the STAT3/NF-κB pathway, promoted tumor growth, and enhanced DDP resistance. In general, CAFs-derived exosomes deliver circZFR to HCC cells, inhibit the STAT3/NF-κB pathway, and promote HCC development and chemoresistance. The results provided a new sight for the prevention and treatment of chemoresistance in HCC. |